Mapping the structural and functional profile of hyaluronic acid hydrogels: a comparative physicochemical analysis

Hyaluronic acid (HA) hydrogels are versatile biomaterials whose performance depends on formulation parameters such as degree of crosslinking and HA concentration. Although widely used in aesthetic and regenerative medicine, few studies correlate composition, microstructure, and viscoelastic parameters to evaluate true in situ mechanical performance. This study provides an integrated structure-function mapping based on the physicochemical and structural comparison of four commercial hydrogel formulations: Dermaxgel® Deep (DMXDEEP), Dermaxgel® Ultradeep (DMXULTRA), Juvederm® Volux (JUVVOL), and Restylane® Lyft (RESLYFT). Swelling capacity, rheological behavior, scanning electron microscopy (SEM), and Fourier-transform infrared spectroscopy (FTIR) were performed to elucidate structure-property relationships. Although all four hydrogels contained identical HA concentrations, significant differences in mechanical and hydration profiles were observed. RESLYFT presented the highest stiffness and the lowest swelling ratio, consistent with a highly crosslinked and compact network. JUVVOL showed the greatest swelling capacity and mechanical strength close to RESLYFT, suggesting a denser yet more hydrophilic matrix. DMXDEEP and DMXULTRA displayed intermediate behaviors, combining elasticity, cohesiveness, and moderate hydration. SEM and FTIR analyses confirmed differences in porosity and crosslinking patterns. Overall, formulation composition and network architecture influenced physicochemical integrity and in situ performance, and the established predictive model supports the development of next-generation HA-based biomaterials.